3-alpha-acyloxy-11-keto-dhomoetiochololactone



s was Patented Oct. 24., 1961 it is now found that the new dodecahydrophenanthrene 3,005,829 compounds of my invention can be prepared by reacting 3-ALPHA-ACYL0XY'11'KET0'D lactones having the structure HOMOETIOCHOLOLACTONE Norman L. Wendler, Summit, N.J., assignor to Merck & Co., Inc., Rahway, N.J., a corporation of New Jersey CH3 No Drawing. Original application Jan. 24, 1955,'Ser.

No. 483,819. Divided and this application July 31, :0 1959, Ser. No. 838,373 (@112) 2 Claims. (Cl. 260-343.2)

This invention relates to novel dodecahydrophenanthrene compounds and processes of preparing the same. Specifically, it is concerned With A -l-carboxyethyl-2,4bfidimethyl-4-keto-7a-hydroxy-4aa,8ap3,l0a,B dodecahydrophenanthrene, A -1-carboxypropyl-2,4b,8-dimethyl-4-keto- 7a-hydroxy-4aa,8afi,10a,6-dodecahydrophenanthrene and derivatives thereof, and with new intermediate products and processes useful in the preparation of these dodecahydrophenanthrene compounds.

wherein in. is 2 or 3 with a base. The lactone employed as the starting material in my process can be saturated or unsaturated and can contain other substituents such as alkyl, hydroxy, keto, acyloxy, and the like.

The desired a,,8-unsaturated acids are produced by reacting the starting lactone with a strong, inorganic base [his apphcauon 1S a dlvlslon of my copendmg apsuch as alkali metal hydroxides or carbonates, alkaline plication Serial No. 483,819 filed January 24, 1955.

. earth metal hydroxides, alkali metal alkoxides, and the In accordance with thls invention, it is now found that like. Genarany, I p f to effect the reaction in the dodecahydmphenanthrene compounds havmg the Struc' presence of a suitable inert solvent for the lactone such tural formula as a lower aliphatic alcohol. The reaction is most conveniently effected by heating a methanol solution of the lactone with an alkali metal hydroxide, for example, sodium or potassium hydroxide, or with an alkali metal alcoholate, for example sodium methylate or potassium gmnouooon ethylate. After the reaction is complete, the desired 04,13-

unsaturated acid can be readily recovered by acidifying the reaction mixture, concentrating the resulting solution to dryness, dissolving the residue in ether ether, and concentrating the resulting solution. The process of the present invention is particularly wherein n is 2 or 3, which are valuable products useful useful in preparing Az 1 Garb0Xyethy1 2,4b|3 dimethy1 4 1n the preparation of steroids such as aldosterone and keto 7a hydroxy 4aa3a510a'8 dodecahydmphenam the like, can be prepared by reactlng compounds having threne and 2 1 pz 4 4 7 the Structural formula hydr0xy-4aa,8a;3,10a,8-dodecahydrophenanthrene, which,

CH: as will be pointed out in detail hereinafter, are very use- 0 ful in the preparation of valuable steroid compounds. These Products are produced by the hydrolysis of 30ahydroxy-11-keto-etiochololactone or acyl derivatives CH (li)H2)n thereof, and 3oc-hydroxy-ll-keto-D-homoetiochololactone or its acyl derivatives respectively.

The novel dodecahydrophenanthrene compounds of the present invention can be readily converted into useful derivatives thereof such as esters in accordance with methods known in the art. Thus, these compounds can wherein is the Same as hove, and R is hydrogen acyl be acylated to form the corresponding 3-acyloxy comwith a base. pounds. For example, the dodecahydrophenanthrene It is an Object of the Present ihvehhoh to Provide 8 compounds can be reacted with acetic anhydride in the Process for the Preparation of novel Az-l-cafboxyethyl presence of pyridine to form the corresponding 3-acetoxy 0r cHIbOXYPTOPYI'dOdCCahYdTOPheIIanthfelie compollhdscompounds, or with benzoyl chloride to produce the cor- Alloihfif Object is to Provide Y Y firespoding 3-benzoxy derivative. Also, the dodecahydro- Y y Y 1 l dodecflhydrophenauthrene compounds, or the 3-acyloxy derivatives Phehailthfehe, YP PY fly thereof, can be readily esterified, for example, by reacy Y- 5, fiy Opheilahthfehe, and tion with an alcohol in the presence of a small amount of derivatives thereof convertible thereto by hydrolysis. A an id, to bt i th corresponding d d h h further object i to provide novel compounds u f l s threne compound having an esterified carboxylic acid intermediates in the preparation of these a,B-unsaturated group,

acids. These and other objects of my invention will be In accordance with another embodiment of my invenapparent from the detailed description hereinafter protion, it is now found that A -1-carboxyethy1-2,4bp-di. vidod, methyl-4-keto 7a hydroxy 4210c,88fi,108.fi dodecahy- In accordance with one embodiment of my invention, drophenanthrene can be prepared from 3a-hydroxy-11,

17-dikeo-etiocholane by the process which can be shown as follows:

In this process the starting material, 3a-hydroXy-11,17- diketo-etiocholane (XI) is reacted with an organic per acid to produce 3a-hydroXy-ll-keto-etiochololactone (XII) which on treatment with a base is converted to the desired dodecahydrophenanthrene compound.

Alternatively, in the above process, the intermediate etiochololactone (XII) can be acylated to produce the 3-acy1oxy derivative which can then be converted to the dodecahydrophenanthrene compound by reaction with a base.

Pursuant to a further embodiment of my invention, I have found that A -1-carboxypropyl-2,4bp-dimethyl- 4 keto 7a hydroxy 4aa,8a, 3,10a,B dodecahydrophenanthrene can be prepared from 3a-acetoxy-11,17-dikcto-etiocholane by the process which can be shown as follows? RO-- HQ- CH3 ?Ha O-COH3 \T CH3 M1 on om ---0N OH CH i HO- RO- v III E CH3 f OH OH RO- i R0 V VI wherein R represents an acyl group.

In accordance with the foregoing flowsheet 3a-acyloxy- 11,17-diketo-etiocholane (I) is converted to the cyanohydrin, of 3a-17 3-dihydroxy-l1-keto-17-isoetianic acid (II); acylation of this compound by reaction with an acylating agent forms the corresponding diacyl derivative (III); reduction of the diacyl derivative by reaction with lithium aluminum hydride and reaction with acetone yields the oxazolidine derivative of 3oc,l l 8,17fi-trihydroxy- ZO-amino-norpregnane (IV); diazotization of this amine by reaction with sodium nitrite in aqueous acetic acid and acylation of the resulting product followed by oxidation with chromic acid affords 3a-acyloxy-11,17a-diketo- D-homoetiocholane (V); oxidation of this compound with an organic per acid produces 3a-acyloXy-11-ketoD- homoetiochololactone; and treatment of this lactone with a strong base afiords A -1-carboxypropyl-2,4b;8-dimethyl- 4 keto 7a hydroxy 4aa,8a;3,10a 8 dodecahydrophenanthrene (VII).

Alternatively, the desired dodecahydrophenanthrene compound can also be prepared using 3a,17a-dihydroxy- 11,20-diketo-2l-acyloxy-pregnane as the starting material by the following reactions:

CH3 CH3 $1120 R (IEHzOH ICO ICH OH ""OH "-011 of OH CHJ i HO- HO-..

VIII IX NHz CH3 CH2 HC=NOH OH 011 0 O- OH CH HO HO XA X accesses wherein R represents an acyl group.

In this series of reactions, the starting material, 30:,17ocdihydroxy-l1,20-diketo-21-acyloxy-pregnane (VIII) is reduced by reaction with lithium aluminum hydride to form the pentol (IX); treatment of this compound with periodic acid followed by treatment of the resulting reaction product yields the oxime (X); and reduction of the oxime with hydrogen in the presence of a noble metal catalyst affords 30,11 8,17u-trihydroxy-20-aminonorpregnane; diazotization of this amine by reaction with sodium nitrite in aqueous acetic acid and acylation of the resulting product followed by oxidation with chromic acid gives 3a-acyloxy-11,l7a-diketo-D-homoetiocholane (V). This compound is then converted to A -1-carboxypropyl 2,4b,8 dimethyl 4 keto 7 hydroxy 48.00, 8a,8,10afi-dodecahydrophenanthrene as described above.

In the above-described methods for the preparation of A 1 carboxypropyl 2 4b,8 dimethyl 4 keto- 700 hydroxy 4aa,8a,6,10afi dodecahydrophenanthrene, although any acyl group can be utilized for the purpose of protecting the hydroxy substituents, I have found it to be particularly advantageous to employ lower fatty acid acylating agents for this purpose. Generally, I prefer to use an acetyl group for the protection of the hydroxy substituents, since these derivatives are most conveniently prepared.

The novel dodecahydrophenanthrene compounds obtained in accordance with the present invention are useful as intermediates in the preparation of valuable steorid compounds. Thus, A 1 carboxyethyl 2,4b,8 dimethyl 4 keto 7a hydroxy 4aa,8a/8,10a/i dodecahydrophenanthrene can be converted to the valuable mineral factor of the adrenal cortex as follows:

The A -l-carboxyethyl 2,4b,8 dimethyl-4-ket0-7a-hydroxy 4aa,8afi,i1Gap-dodecahydrophenanthrene is acetylated by reaction with acetic anhydride to form the 7a-acetoxy derivative; this derivative is then esterified by reaction with methanol in the presence of HCl to form the corresponding methyl ester; reaction of this methyl ester with N-bromosuccinimide followed by treatment of the reaction product with potassium acetate in acetone and hydrolysis of the resulting reaction product yields A 7 a hydroxy 4-keto-2-(hydroxymethyl)Abe-methyl- 4aa,8a,8,10a,8 dodecahydrophenanthryl 1,8 propionic acid; oxidation of this product with manganese dioxide and treatment of the oxidized product with methanol in the presence of acid produces A -7a-hydroxy-4-keto- 2 (dimethoxy methyl)-4bfl-methyl 42oz; 8a;8,10aB-dodecahydrophenenanthryl-lfi-propionic acid; acetylation of this product with acetic anhydride and treatment of the acetylated product with thionyl chloride affords A -7aacetoxy 4 keto Z-(dimethoxymethyl)-4bfl-methyl-4aa, 8a,8,10a,8 dodecahydrophenanthryl 1/3 propionic acid chloride; reaction of compound with diazomethane produces A 7a acetoxy-4-keto-2 (dimethoxymethyl)- 4bp methyl 4aa,8-afi,10afi dodecahydrophenanthryl- ,B-propiodiazomethyl ketone; treatment of this compound with acetic acid yields 3a,17 a-dihydroxy-11,17-diketo- 18,18-dimethoxyD-homoetiochlolane; oxidation of this compound with sodium meta-periodate followed by air oxidation and acetylation of the oxidized product with acetic anhydride in the presence of pyridine affords 30cacetoxy-18,18-dirnethoxy-1l-keto-etiobilianic acid; esterification of the latter product with methanol in the presence of a small amount of acid and treatment of the esterified product with sodium ethylate results in obtaining 3rx-hydroxy-11,17-diketo-18,18 dimethoxy-etiocholane; reaction of this product with potassium acetylide in liquid ammonia followed by catalytic reduction afiords 3u,17-dihydroxy-11-keto-18,18 dimethoxy 17 vinyletiocholane; bromination of this product with phosphorous tribromide followed by treatment of the brominated product with potassium acetate produces A -3a-hydroxy- 11-ket0 18,18-dimethoxy-21-acetoxy-pregnene; reaction of this product with osmium tetroxide and treatment of the resulting osmate ester with acetic anhydride yields 3oc,2(),21 triacetoxy 11 keto 17a-hydroxy-l8,18-dimethoxy-pregnane; reaction of this product with zinc in toluene and hydrolysis of the resulting product with an alkali affords 3u,2l1-dihydroxy-11,20-diketo18,18-dimethoxy-pregnane; treatment of this compound with N-bromoacetamide followed by acetylation of the resulting reaction product with acetic anhydride in the presence of pyridine, reaction of the acetylated product with bromine, and the treatment of the resulting brominated product with semicarbazide affords A -3,11,20-tniketo-18,18dimethoxy- 21-acetoxy-pregnane-3,ZO-bissemicarbazone, reduction of this product with sodium borohydride, and hydrolysis of this reduced product with pyruvic acid affords aldosterone 21-monoacetate.

The A 1 carboxypropyl 2,4'b-dimethyl-4-keto-7w hydroxy-4aa,8a5,10aB-dodecahydrophenanthrene can be converted to the corresponding l-carboxyethyl compound by the Barbier-Wieland method, and the product so obtained can be converted to aldosterone 21-monoacetate by the procedures described above.

The following examples are presented to illustrate the methods of preparing the new compounds of the present invention.

EXAMPLE 1 Preparation of A -1-carb0xyethyl-2,4b-dimethyl-4-ket0- 7a hydroxy 4au,8afi,10a5 dodecahydrophenanthrene from fiot-hydroxy-ll -keto-eti0ch0lolact0ne To 0.5 g. of 3cc-hYdTOXY-1l-kdl'tO-GUOChOlMllOIlE in 10 ml. of refluxing methanol was added over the course of one hour 5.2 ml. of 0.27 N methanolic sodium methoxide. Removal of the methanol in vacuo and addition of ether afforded the sodium salt of M-l-carboxyethyl-ZAb-dimethyl 4 keto 7 a-hydroxylaafiafi,l0afl-dodecahydrophenanthrene which was filtered, washed with ether and dissolved in a few ml. of water. Addition of dilute hydrochloric acid followed by ether extraction in the usual way gave the crystalline unsaturated acid which was recrystallized from acetone petroleum ether; glistening plates 350 mg, M.P. 178-9"; 50 mg, M.P. 174-6"; corrected yield, 89%. Further recrystallization did not raise the M.P. above l789; [a1 32.5 (C=0.79);

igg 237 m e=12,100; ANLUOI 3-4, 5.87, 6.00, 6.12,

max.

Analysis.Calcd. for C H O C, 71.23; H, 8.81. Found: C, 70.57; H, 8.79.

Preparation of 3u-hydr0xy-11-ket0-eti0chol0act0ne The starting material used in the foregoing example can be prepared from 3a-acetoxy-11,20-diketo-17a-hydroxy-pregnane as follows:

To a solution of 3u-acetoXyDLZO-diKetO-I7a-hydroxy pregnan-e, M.P. 2025 C. (60 g.) in acetic acid (600 ml.) was added chromic oxide (11.3 g.; equivalent ratio 1.121) in water (5 ml.) and acetic acid ml); After three days at 25 C. the solvent was removed in vacuo, water added and the product extracted with ethyl acetate. The organic solution was washed with 5% aqueous sodium carbonate and water and dried over anhydrous magnesium sulfate. The residue remaining after removal of the solvent was dissolved in 2:1 petroleum ether-benzene (1200 ml.) and chromatographed on acidwashed alumina (500 g.). The column was eluted with petroleum ether-benzene, benzene and benzene-chloroform mixtures. From the petroleum ether-benzene fractions there was obtained 3a-acetoxy11,17-diketo etiocholane; 21.5 g., M.P. 159-161 C. and 6.5 g., M.P. 156-9 C.

3es-acetoxy-11,17-diketo etiocholane (14.0 g.) was dissolved in a solution of sodium hydroxide ("12.0 g.) in 50% methanol (240 ml). After 30 minutes at 25 C. acetic acid (18 ml.) was added, the mixture was concentrated to 150 ml. and water (300 ml.) was added. The precipitated 3whydroxy-11,17-diketo-etiocholane was filtered, washed several times with water and dried in vacuo; 12.2 g., M.P. 1868 C.

To a solution of 3a-hydroxy- 11,17-diketo-etiocholane (I) (15.0 g.) in benzene (225 ml.) was added perbenzoic acid in benzene (100 ml., 0.32 M). After 48 hours at room temperature'the mixture was concentrated in vacuo to a thick slurry, triturated with ether (75 ml.); filtered and washed with ether. Crystallization from acetone ether gave 3e-hydroxy-ll-keto-etioohololactone as massive prisms 7.3 g., M.P. 2128 C., 3.4 g., M.P. 2026 C. (75%). Recrystallization from acetone-petroleum ether raised the melting point to 216-220 C.; [a1 12 Analysis.C-alcd. for C H O C, 71.23; H, 8.81. Found: C, 71.65; H, 9.05.

EXAMPLE 2 Preparation of A -l-carboxyethyl-2,4b-dimethyl-4-keto- 7a. hydroxy 4aa,8afi,10afi dodecahydrophenanthrene from 3a-acet0xy-11-ket0-eti0chol0lact0ne Preparation of 3a-acet0xy11-ket0-eti0ch0l0lact0ne The starting material used in the foregoing example is prepared from 3a-acetoxy-11,17-diketo-etiocholane as follows:

To a solution of 3a-acetoxy-11,17-diketo-etiocholane (1.73 g.) in 5 ml. of acetic acid was added a solution of peracetic acid in acetic acid (4.8 ml., 1.25 M), and the colorless mixture was kept at 25 C. for 24 hours. Slow addition of 100 ml. of cold water precipitated 3a-acetoxyll-keto-etiochololactone in the form of elongated prisms melting at 181-184 C.; [oc] +14 (C=0.77);

OHCI maX. a

Analysis.-Calcd. for C H O C, 69.58; H, 8.34. Found: C, 69.24; H, 8.10.

EXAMPLE 3 Preparation of A -I-carb0xypr0pyl-2,4b-dimethyl-4-ket0- 7a hydroxy 4aa,8a;8,10ap-dodecahydrophenanthrene from 3oc-acez0xy-11-ket0-D-h0m0eti0chololacz0ne A solution of Zia-acetoxy-l1-keto-D-homoetiochololactone (188 mg.) in methanol (20 ml.) and aqueous 1.00 N sodium hydroxide (1.50 ml.) was refluxed one hour under nitrogen. Acetic acid (0.5 ml.) was added, the solvent removed in vacuo and the acidic product extracted into ether and worked up in the usual way. It crystallized spontaneously on removal of solvent and was max. 7 1118K.

Analysis.-Calcd. for C H O C, 71.81; H, 9.04. Found: C, 71.70; H, 8.79.

EXAMPLE 4 Preparation of 3a-acet0xy-11-ket0-D-h0moetiochololactone from 30,17oc dihydroxy-Il,ZO-diketo-ZJ-acet0xy pregnane The starting material use in Example 3 is prepared from 3a-17a-dihydroxy-11,20-diketo-21-acetoxy pregnane as follows:

A solution of 6 g. of 3a,17u-dihydroxy-11,20-diketo- 21-acetoxy pregnane in 600 ml. of tetrahydrofuran was reduced with 6 g. of lithium aluminum hydride. Addition was effected at room temperature after which the reaction mixture was refluxed for 1 /2 hours. The excess lithium aluminum hydride was decomposed with ethyl acetate followed by 200 ml. of a saturated solution of sodium sulfate and 200 g. of magnesium sulfate. The reaction mixture was filtered and the filtrate evaporated to give 6 g. of 35,11,17a,20,21-pentahydroxy pregnane.

The crude pentol (6 g.) in 250 ml. of dioxane was treated with 3.72 g. of periodic acid (H 10 in 70 ml. of water and the reaction solution allowed to stand for 4 hours. At the end of this period the reaction mixture was evaporated to near-dryness, the residue extracted with ether and the ether extract washed with water and evaporated to an oil. This oil was dissolved in n11. of methanol and treated with 2.5 g. of hydroxylamine hydrochloride and 3 g. of sodium acetate in 10 ml. of Water, heated to boiling on a water bath and allowed to stand overnight at room temperature. The reaction mixture from the oximation was evaporated nearly to dryness, the residue dissolved in ether and the oxime 311,171 dihydroxy-l1-keto-20-oxirnino-2l-norpregnane extracted with 10% aqueous sodium hydroxide. Acidification of the alkaline extracts with hydrochloric acid deposited the crude oxime as a gum. The latter was taken up in etherethyl acetate, dried over magnesium sulfate and evaporated to give 3.8 g. of the oxime as an amorphous residue.

A solution of 2.8 g. of the above oxime in 50 cc. of acetic acid was hydrogenated at atmospheric pressure and room temperature using 280 mg. of platinum oxide. The uptake of hydrogen was rapid and conformed to essentially 1 mole. The catalyst was filtered off and the filtrate containing the 306,170: dihydroxy 11 keto20- amino-21-norpregnane made ca. 50% with water, then treated dropwise at 0 C. with a solution of 1 g. of sodium nitrite in 30 ml. of water. The reaction product, which had largely separated (1.6 g.) during the overnight reaction period was acetylated with acetic anhydride and pyridine followed by chromic acid oxidation and chromatographed over acid washed alumina. From the 12% ether in benzene eluates was obtained 340 mg. of Sa-acetoxy-l1,17a-diketo-D-homoetiocholane, M.P. 164.5-165.5 C. The 10% ether-benzene eluates yielded 50 mg. of 3a'acetoxy-l1,17-diketo-D-homoetiocholane, M.P. 2036 C.

3a-acetoxy-11,17a-diketo-D-homoetiocholane (1.08 g.) in benzene (14 ml.) was mixed with perbenzoic acid in benzene (19.2 ml. 0.391 M). After 3 days at 25 the remaining per acid was destroyed and the reaction mixture worked up by addition of water and either extraction. The product 3a acetoxy ll-keto-D-homoetiochololactone was crystallized from ether; 760 mg., M.P. -2 C.; 102 mg, M.P. 163.6 C. Recrystallization from ether-petroleum ether gave plates M.P. 172-4 C.; [a1 -24 (C=0.77);

I J Analysis.Calcd. for (322113205: C, H, 8.57.

Found: C, 69.78; H, 8.31.

EXAMPLE Preparation of 3a-acetoxy-l1-ket0-D-homoetioch0l0lactone from 3a-acet0xy-1L17-diket0eti0ch0lan'e 3zx-acet0xy-11,17-diketoeticcholane (5 g.) in 150 cc. of ethanol was cooled to 0 and treated with 30 g. of potassium cyanide, followed by dropwise addition of 34 ml. of glacial acetic acid at such a rate that the temperature did not exceed 58 C. After the completion of addition of acetic acid the reaction mixture was allowed to stir at 0 C. for one hour and at room temperature for two hours. At the end of this digestion period the reaction mixture was added to 5 volumes of water and the precipitated oily product extracted with ethyl acetate. The ethyl acetate extract was washed with Water, dried over magnesium sulfate and concentrated in vacuo to an oil. The oily 3a,17-dihydroxy-1l-keto-l7-cyanoetiocholane was acetylated at room temperature for hours with 25 cc. of pyridine and 10 cc. of acetic anhydride. The acetylation reaction product was treated with excess ice-water and the product extracted with ethyl acetate. The ethyl acetate solution was Washed with dilute aqueous HCl and NaI-ICO solution, dried over magnesium sulfate, concentrated and crystallized from ethyl acetatepetroleum ether to produce 3u,17B-diacetoxy-11-kefuol7a-cyano-etiocholane, M.P. 183-5 C.

A solution of two grams of this cyanohydrin acetate was dissolved in 50 cc. of benzene and treated with 2 g. of lithium aluminum hydride in 250 cc. of ether. The reaction mixture was refluxed for 1 hour and then the excess lithium aluminum hydride cautiously decomposed with water. The solid was filtered, dried in a vacuum desiccator and then extracted with acetone in a Soxhlet extractor for 5-6 hours. Evaporation of the acetone left an oil. The latter was taken up in ether and extracted with dilute HCl. Neutralization of the HCl extract deposited the oxazolidine derivative of 304,110,175- trihydroxy -amino-21-norpregnane which was crystallized from ethyl acetate petroleum ether, melting at 190- 192 C.

Analysis.-Calcd. for C H O N: C, 73.20; H, 10.32; N, 3.72. Found: C, 73.45; H, 10.29; N, 3.73.

A solution of 1 g. of the above amine in 95 ml. of 5% aqueous acetic acid was chilled to 0 C. and treated with a solution of 0.35 g. of sodium nitrite in 8 cc. of water. The reaction mixture was allowed to stand 3 hours at 0 C. and overnight at room temperature. During this period 0.6-0.7 g. of solid product separated. The latter was acetylated with 4 m1. of pyridine and 2 ml. of acetic anhydride at room temperature overnight followed by oxidation in 5 ml. of acetic acid containing mg. of chromic acid. Chromatography of the product on acidwashed alumina yielded from eluates of 15% ether in benzene, 340 mg. of 3oc-acetoxy-l1,17a-diketo-D-homoetiocholane as needles from acetone-petroleum ether, M.P. 1678 C.; [M +28.7 (C=1.02).

Analysis.Calcd. for C H O C, 73.33; H, 8.88. Found: C, 73.50; H, 8.77.

2,4 dinitrophenylhydrazone crystallized as yellow needles from methanol-ethyl acetate, M.P. 220-225 C.

Analysis.-Calcd. for C28H330I1N4I N, 10.37. Found: N, 10.48.

The eluates from the chromatography consisting of 1020% ether in benzene yielded 52 mg. of Ba-acetoxy- 1l,17-diketo-D-homoetiocholane as plates from acetoneether, M.P. 205-7 C.; [a1 +23.0 (C=1.09).

Analysis.Calcd. for C H O C, 73.33; H, 8.88. Found: C, 73.29; H, 8.91.

2,4-dinitrophenylhydrazone crystallized as needles from methanol-ethyl acetate, M.P. 2813.

Analysis.Calcd. for C H O N N, 10.37. Found: N, 10.54.

The 3a-acetoxy-11,17a-diketo-D-homoetiocholane was then treated following the method described in Example 4 to obtain 3a acetoxy-l1,l7oc-diketo-D-homoetiochololactone.

Various changes and modifications of the invention can be made and, to the extent that such variations incorporate the spirit of this invention, they are intended to be included within the scope of the appended claims.

I claim:

1. 3a-acyloxy 11-keto-D-homoetiochololactone wherein the acyl group represents lower alkanoyl.

2. 3a-acetoxy-11-keto-D-homoetiochololactone.

References Cited in the file of this patent UNITED STATES PATENTS 2,755,289 Picha July 17, 1956 

1. 3A - CYCLOXY-11-KETO-D-HOMOETHIOCHOLOLACTONE WHEREIN THE ACYL GROUP REPRESENTS LOWER ALKANOL. 